The long-term goal of the Cancer Genetics and Epigenetics (CGE) Program is to pursue basic research on fundamental cellular processes relevant to cancer biology and to seek opportunities for translating the resulting information into clinical use. To this end, the following Specific Goals will be pursued: 1. Identify the molecular processes by which genomic instability is generated and contributes to oncogenesis; 2. Explore how epigenetic modifications of DMA and chromatin influence tumor initiation and progression; and 3. Elucidate the mechanisms underlying control of cell division and ascertain how these mechanisms are abrogated in cancer. The CGE Program is one of the two Basic Science Programs of the HICCC. In replacing the former Developmental Biology & Genetics Program it has been restructured to increase cancer relevance, and the heightened cancer focus of the new CGE Program is reflected by a 400% increase in NCI funding. The Program pursues its scientific goals by promoting interactions among CGE investigators and with other HICCC members, encouraging collaborative research projects and joint grant proposals, and providing a forum in which CGE investigators share their latest discoveries and consider the clinical value of their basic research findings. Potential clinical applications include identification and analysis of environmental toxins, modified therapeutic regimens to accommodate radiation bystander effects, development of biodosimetry, use of nanofluidic cassettes (biochips) in diagnostic/predictive laboratory assays (including monitoring therapeutic responses), high-throughput screening to identify small molecules that modulate malignant processes, and pre-clinical testing of these molecules for therapeutic effects. The CGE Program consists of 32 members (all full members of the HICCC) from eleven departments at Columbia University. The Program is supported by several collaborative efforts, including a recently renewed, five-year $5.2M (direct costs) program project grant from the NCI entitled Radiation Bystander Effects: Mechanisms (P.I., Tom Hei). For the last budget year of the grant (July 1, 2006 - June.30, 2007), the CGE Program received a total of $17.12M (direct costs) in cancer-relevant grant support, including $3.69M (direct costs) in NCI funding, $12.95M (direct costs) in other cancer-related peer-reviewed funding, and $0.48M (direct costs) in cancer-related non-peer-reviewed funding. The total number of cancer-related publications by the current Program members since the previous submission (i.e., 2003-present) was 330, with 17.0% inter-programmatic and 12.4% intra-programmatic publications.